Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa

Lin Jin; Mahendra P. Kashyap; Yunjia Chen; Jasim Khan; Yuanyuan Guo; Jari Q. Chen; Madison B. Lee; Zhiping Weng; Allen Oak; Prasanth Patcha; Tiffany Mayo; Rajesh Sinha; Venkatram Atigadda; Shahid M. Mukhtar; Jessy S. Deshane; Chander Raman; Carly Elston; Boni E. Elewski; Craig A. Elmets; Mohammad Athar

iScience (Jun 2023)

Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa

Lin Jin,
Mahendra P. Kashyap,
Yunjia Chen,
Jasim Khan,
Yuanyuan Guo,
Jari Q. Chen,
Madison B. Lee,
Zhiping Weng,
Allen Oak,
Prasanth Patcha,
Tiffany Mayo,
Rajesh Sinha,
Venkatram Atigadda,
Shahid M. Mukhtar,
Jessy S. Deshane,
Chander Raman,
Carly Elston,
Boni E. Elewski,
Craig A. Elmets,
Mohammad Athar

Affiliations

Lin Jin: Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Mahendra P. Kashyap: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Yunjia Chen: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jasim Khan: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Yuanyuan Guo: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jari Q. Chen: Hoover High School, Hoover, Birmingham, AL 35244, USA
Madison B. Lee: School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Zhiping Weng: Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Allen Oak: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Prasanth Patcha: Division of Plastic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Tiffany Mayo: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Rajesh Sinha: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Venkatram Atigadda: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Shahid M. Mukhtar: Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jessy S. Deshane: Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Chander Raman: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Carly Elston: Department of Dermatology and Dermatopathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Boni E. Elewski: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Craig A. Elmets: Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Mohammad Athar: Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 6
p. 106896

Abstract

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Summary: Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5′-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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